Ricin is a plant toxin which is an extremely potent inhibitor of protein synthesis. Ricin is an enzyme which contains two specialized chains, one for the enzymatic inactivation of the 60S ribosomal subunit and one for the binding of the toxin to galactose-containing-cell surface receptors of eucaryotic cells. No added cofactors are required to result in inhibition of ribosome activity. Ricin is capable of preferentially inhibiting protein synthesis in tumor cells. Even though ricin is an enzyme, we can demonstrate the stoichiometric binding of ricin and ricin A chain, the enzymatically active polypeptide, to 60S ribosomal subunits. Evidence suggests that the site of enzymatic inactivation on the ribosome is near or identical to the stoichiometric binding site. This proposal outlines procedures to identify these two sites and to eventually discover the molecular mechanism by which ricin inactivates the 60S ribosomal subunit of rat liver.